Recommendations for the diagnosis and management of persons with suspected vaccine-induced immune thrombotic thrombocytopenia (VITT) / Recomendaciones para diagnostico y manejo de personas con trombocitopenia trombotica inmune inducida por vacunas (VITT)

Abstract In recent months, rare cases of thrombosis at unusual sites associated with thrombocytopenia, occurring within a typical risk window (i.e., 4-28 days) after receiving SARS CoV2 vaccines, have been reported. Healthcare professionals should be prepared to detect these cases on time. The Expert Panel of the Knowledge Management and Transfer Network conducted a free search of the related literature. With the available information and the clinical expertise of the working group, we formulated, reviewed, and endorsed recommendations for the timely suspicion, diagnosis (case definitions, the use of initial laboratory and imaging tests, specific tests), and management of these thrombotic conditions. This document is considered a living document that will be updated as new evidence emerges, and recommendations may change over time.

Resumen En meses recientes se han reportado casos raros de trombocitopenia y trombosis en sitios inusuales, que ocurren dentro de una ventana de riesgo típica ( por ejemplo de 4 a 28 días) luego de recibir vacunas de SARS CoV 2. Los profesionales de la salud deben estar preparados para detectar estos casos a tiempo. Un panel de expertos y una red de transferencia de conocimiento realizó una búsqueda libre de literatura seleccionada. Con la información disponible y la experticia clínica del grupo de trabajo revisamos y dimos recomendaciones para la sospecha temprana, el diagnostico (definición de caso, el uso de pruebas de laboratorio especificas y de imágenes diagnósticas) para le manejo de estas condiciones tromboticas. Este documento es considerado un documento vivo que debe ser actualizado a medida que surja nueva evidencia y las recomendaciones vayan cambiando con el tiempo

[Treatment of cancer and thrombosis: practical approach]. / Tratamiento de cáncer y trombosis: enfoque práctico.

Individuals with cancer are at increased risk of developing thrombosis. The prevalence of thrombosis depends on tumor-related factors such as histological type, stage, the use of central venous catheters, or treatment with surgery, chemotherapy or radiotherapy, as well as general prothrombotic factors including advanced age, immobility, obesity, hereditary thrombophilias and comorbidities. Prophylactic or therapeutic treatment of thrombosis should be individualized and will depend on both the risk of thrombosis and bleeding. In this review we intend to update concepts that have changed substantially such as green food-free diet, or the indication of absolute bed rest in patients with recent thrombosis. We propose evidence-based therapeutic strategies regarding the most prevalent clinical problems encountered in patients with cancer and thrombosis.

In vivo assessment of hemocompatibility of a ventricular assist device in healthy swine.

OBJECTIVE: To assess the hemocompatible performance of a novel implantable pneumatic ventricular assist device (VAD, Innovamédica, México) in healthy swine. The aim of this pilot study was first, to determine if short-term VAD implantation elicited remarkable inflammatory response above that expected from surgical trauma; and second, to assess if heparinized or passivated VAD coatings, in combination with systemic anticoagulant or antiaggregant therapies, modified the VAD's hemocompatible performance. METHODS: Hemodynamic, physicologic, inflammatory and histological parameters were measured in 27 pigs receiving VAD support for six hours, testing combinations of heparinized or passivated VAD coatings and systemic anticoagulant/ antiaggregant therapies. Mean concentrations of interleukin -1 B (IL-1B), interleukin -6 (IL-6), C-reactive protein (CRP), or thrombin-antithrombin III (TAT) complexes (coagulation indicator) were measured from blood. ANOVA statistics were employed. RESULTS: No substantial increases in mean IL -1B, IL-6, CRP, or TAT were obtained during VAD support. Hemodynamic ans physiologic parameters were normal. We found no evidence of thromboembolisms or micro-infarctions in heart and lung samples. No major coaguli/deposits were found in VAD compartments. Overall, no remarkable differences in measurements were found using heparinized, passivated, or uncoated VAD, or with systemic anticoagulation, antiaggregant therapy, or no treatment. CONCLUSIONS: Our findings demonstrate, firstly, that during the time-period tested, the VAD elicited negligible inflammation above the effects of surgical trauma; and secondly, that little coagulation was observed upon VAD support in any of the cases tested. Contemplating further validation studies, our data indicate that the Innovamédica VAD is a highly hemocompatible system.

In vivo assessment of hemocompatibility of a ventricular assist device in healthy swine / Evaluación de la hemocompatibilidad in vivo (cerdos sanos) de un dispositivo de asistencia ventricular

Objective: To assess the hemocompatible performance of a novel implantable pneumatic ventricular assist device (VAD, Innovamédica, México) in healthy swine. The aim of this pilot study was first, to determine if short-term VAD implantation elicited a remarkable inflammatory response above that expected from surgical trauma; and second, to assess if heparinized or passivated VAD coatings, in combination with systemic anticoagulant or antiaggregant therapies, modified the VAD's hemocompatible performance. Methods: Hemodynamic, physiologic, inflammatory and histological parameters were measured in 27 pigs receiving VAD support for six hours, testing combinations of heparinized or passivated VAD coatings and systemic anticoagulant/ antiaggregant therapies. Mean concentrations of interleukin-1 β (IL-16), interleukin-6 (IL-6), C-reactive protein (CRP), or thrombin-antithrombin III (TAT) complexes (coagulation indicator) were measured from blood. ANOVA statistics were employed. Results: No substantial increases in mean IL-1β, IL-6, CRP, or TAT were obtained during VAD support. Hemodynamic and physiologic parameters were normal. We found no evidence of thromboembolisms or micro-infarctions in heart and lung samples. No major coaguli/deposits were found in VAD compartments. Overall, no remarkable differences in measurements were found using heparinized, passivated, or uncoated VAD, or with systemic anticoagulation, antiaggregant therapy, or no treatment. Conclusions: Our findings demonstrate, firstly, that during the time-period tested, the VAD elicited negligible inflammation above the effects of surgical trauma; and secondly, that little coagulation was observed upon VAD support in any of the cases tested. Contemplating further validation studies, our data indicate that the Innovamédica VAD is a highly hemocompatible system.

Objetivo: Evaluar la hemocompatibilidad de un nuevo dispositivo de asistencia ventricular (DAV, Innovamédica, México) neumático e implantable, en cerdos sanos. En este estudio piloto se propuso determinar primero, si la implantación a corto plazo del DAV suscitaría una respuesta inflamatoria por encima de aquella esperada tras trauma quirúrgico; segundo, evaluar si recubrimientos heparinizados o pasivos del DAV, en combinación con tratamientos sistémicos anticoagulantes o antiplaquetarios, modificarían la hemocompatibilidad del DAV. Métodos: Se midieron parámetros hemodinámicos, fisiológicos, inflamatorios e histológicos en 27 cerdos recibiendo soporte del DAV durante seis horas, evaluando combinaciones de recubrimientos heparinizados y pasivos del DAV, y terapias sistémicas anticoagulantes / antiplaquetarias. Se obtuvieron, a partir de sangre, las concentraciones promedio de interleucina-1 (IL-1β), interleucina-6 (IL-6), proteína C reactiva (PCR) y los complejos trombina-antitrombina III (TAT) (índice de coagulación). Se emplearon análisis estadísticos ANOVA. Resultados: No se observaron incrementos importantes en los niveles promedio de IL-1β, IL-6, PCR, o TAT durante soporte del DAV. Los parámetros hemodinámicos y fisiológicos fueron normales. No existió evidencia alguna de trom-boembolias o micro-infartos en muestras de miocardio y pulmón. No se encontraron coágulos o depósitos mayores en compartimentos del DAV. En general, no se apreciaron diferencias notables de mediciones utilizando dispositivos con recubrimiento heparinizado, pasivo o sin recubrimiento, en conjunto con terapia sistémica anticoagulante, antiplaquetaria o sin ella. Conclusiones: Nuestros hallazgos demuestran, primero, que durante el periodo de medición experimental, el DAV suscitó una respuesta inflamatoria mínima por encima de los efectos de trauma quirúrgico, y; segundo, en todos los casos evaluados, se observaron escasos o inexistentes efectos de coagulación durante soporte ventricular. Contemplando estudios adicionales de validación, nuestros datos indican que el DAV Innovamédica es un sistema altamente hemocompatible.

Crosstalk between coagulation and inflammation during Dengue virus infection.

Dengue fever is the most prevalent viral disease transmitted by vectors (Aedes aegypti, Aedes albopictus) in worldwide. More than 100 million cases occur annually with a mortality rate of 5% and no safe vaccine is available. The pathogenesis of Dengue, where host and viral factors participate in the establishment of Dengue haemorrhagic fever (DHF) and Dengue shock syndrome (DSS) remains unresolved. Clinical observations have revealed significant abnormalities in coagulation and inflammation systems, with increased levels of tissue factor (TF) and the chemokine IL-8, correlating with the severity of the disease and implicating damage to endothelial vascular cells (EVC). Here we present novel insights concerning the crosstalk between the regulatory signaling pathways of the coagulation-inflammation processes, during Dengue virus (DV) infection of EVC. We found that DV up-regulates Protease Activated receptor type-1 (inflammation) and TF (coagulation) receptors, via the phosphorylation of p38 and ERK1/2 MAPKs, which favor the activation of NF-kappaB transcription factor. This induces pro-inflammatory (IL-8) or pro-adhesive (VCAM-1) gene expression which may lead to EVC activation. The elucidation of the basic principles that signal these processes has important implications for the design of new therapeutic strategies for DHF/DSS.

Cytochrome P4501A1 polymorphisms in the Amerindian and Mestizo populations of Mexico.

Several polymorphisms in the CYP1A1 locus have been identified and their genotypes appear to exhibit population frequencies that depend on ethnicity. We studied two CYP1A1 polymorphic sites (position 4889 and 6235) in a group of 212 unrelated healthy individuals belonging to three different Mexican populations (106 Mexican Mestizos, 52 Teenek and 54 Mayos). Comparison among Mexican populations showed increased frequency of the *Ile allele (A on position 4889) in Mexican Mestizos when compared to Amerindians (p < 0.05). The analysis of position 6235 showed increased frequencies of *m2 (C in this position) allele in Teenek when compared to Mestizos and Mayos (p < 0.05) and of *m2/*m2 genotype when compared to Mestizos (p < 0.05). Amerindian populations (from Mexico and South America) presented the lowest frequencies of *Ile (position 4889) and *m1 (position 6235) alleles, however these frequencies vary according to the ethnic group studied. Mexican Amerindian groups together with other South Amerindian populations showed the highest frequencies for *Val at position 4889 and the *m2 allele at position 6235. The present study corroborates the high frequencies of*Val and *m2 alleles in the Amerindian populations and detects some differences between Mexican populations that correlate with linguistic differences. Our data could be helpful in understanding the distribution of these polymorphisms and in clarifying their roles as genetic and evolution markers in Amerindian populations.

Increased fibrin polymerization rate in patients with primary antiphospholipid syndrome and systemic lupus erythematosus.

The main event in blood coagulation is the thrombincatalyzed conversion of fibrinogen into fibrin. This singular transformation of a soluble protein into an insoluble polymeric network occurs with faultless precision. Abnormalities of fibrin polymerization can lead to hemorragic and thrombotic disorders. Increased fibrinogen plasma concentration (Fg) and fibrin polymerization rate (FPR) could be additional risk factors associated with atherothrombosis in antiphospholipid syndrome (APS) and in systemic lupus erythematosus (SLE). Our objective was to investigate Fg and FPR in consecutive patients with APS and SLE. Thirty-nine patients and 31 age- and gender-matched healthy controls were studied. Sixteen patients had primary APS, 13 patients had SLE, and 10 patients had SLE plus APS. The mean of the FPR was significantly increased (0.2799 +/- 0.091) in patients with APS plus SLE as compared with the control group (0.2052 +/- 0.055) (p < 0.05). Fg was higher in APS plus SLE (3.15 g/L +/- 0.43) and in primary APS (3.03 g/L +/- 0.29) than in controls (2.87 g/L +/- 0.49). Our results demonstrated an increased FPR in patients with APS plus SLE. This phenomenon could be an additional risk factor for thrombosis in these autoimmune diseases.

Diferencias hematológicas entre los efectos de las bombas de rodillo y centrífuga / Hematologic differences caudes by centrifugal vs. roller pump in extracorporeal circulation

Una de las complicaciones secundarias a la utilización de la circulación extracorpórea, es el sangrado postoperatorio debido al daño a los elementos formes de la sangre y a la activación de las diferentes cascadas, entre ellas coagulación, fibrinólisis y complemento. Se realizó un estudio prospectivo con el objetivo de evaluar el comportamiento de los elementos formes sanguíneos y factores de coagulación durante la circulación extracorpórea con bomba centrífuga contra bomba de rodillo. Se evaluó asimismo el consumo de los productos sanguíneos y se cuantificó el consumo de los productos transfundidos. En relación a las características demográficas no hubo diferencia entre ellos, el tiempo de by-pass cardiopulmonar fue menor a los 85 minutos, el flujo sanguíneo en la bomba centrífuga se mantuvo en promedio de 3.6 l contra 3.37 l que otorga la bomba de rodillo, siendo esto estadísticamente significativo. Las variables hematológicas fueron comparadas entre ambos grupos, no existiendo diferencias estadísticamente significativas. Sin embargo, el factor VIII, el fibrinógeno y las plaquetas presentan una tendencia a mantenerse en mayor cantidad que en el grupo control(rodillo). Por lo tanto: 1.- Existe una tendencia de conservación del factor VIII, número de plaquetas y preservación de fibrinógeno en los pacientes sometidos a biobomba. 2.- No existe diferencia significativa entre el número de unidades transfundidas, requeridas en el grupo de biobomba, contra el grupo de rodillo. 3.- Los pacientes sometidos a biobomba se encuentran mejor perfundidos durante la circulación extracorpórea. 4.- No existe diferencia en relación a la cantidad de sangrado en 24 hs entre el grupo de biobomba contra el grupo de rodillo

Reservas hepáticas de hierro y nivels de perritina en suero de pacientes alcohólicos y no alcohólicos con hepatopatias crónicas / Hepatic iron stores and serum ferritin levels in alcoholic and non-alcoholic patients with chronic liver diseases

Con el objeto de evaluar la utilidad de la ferritina en suero (Ft) como indicador de reservas de hierro de pacientes alcohólicos y no alcohólicos con hepatopatías clínicas se estudiaron 35 pacientes: 18 con cirrosis o fibrosis alcohólica y 17 con padecimientos hepáticos de etiología diversa, no alcohólicos. Los pacientes alcohólicos tenían 3 a 32 meses de abstinencia alcohólica. Las reservas de hierro se establecieron mediante la cuantificación de hierro no hemínico (HNH) en biopsia hepática. En 8 casos del grupo de alcohólicos (44%) y en 4 de los no alcohólicos (23%) el HNH estuvo por arriba de muestras cifras de referencia (> 48 mg/100 g en varones y > 20 mg/100 g en mujeres). En los pacientes alcohólicos se obtuvieron correlaciones directas significativas entre Ft y ALAT y Ft vs, bilirrubina total, mientras que estas correlaciones inversas y no significativas en los no alcohólicos. La correlación entre HNH y Ft fue estadísticamente significativa en los no alcohólicos (r = 0.667), pero fu más baja en los alcohólicos (r = 0.478). Concluimos que: a) la siderosis hepática, descrita en una proporción considerable de los bebedores activos, permanece en los alcohólicos que tienen 3 o más meses de abstinencia alcohólica, b) en individuos con hepatopatías crónicas no alcohólicos la Ft aparentemente sí refleja reservas de hierro, c) en los alcohólicos la inflamación o necrosis hepática modifica los niveles de Ft, por lo tanto este parámetro no es útil para establecer las reservas de hierro en estos pacientes